Peptic ulcer disease (PUD), also known as a peptic ulcer or stomach ulcer, is a break in the lining of the stomach, first part of the small intestine, or occasionally the lower esophagus.[1][2] An ulcer in the stomach is known as a gastric ulcer while that in the first part of the intestines is known as a duodenal ulcer. The most common symptoms are waking at night with upper abdominal pain or upper abdominal pain that improves with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people have no symptoms.[1] Complications may include bleeding, perforation, and blockage of the stomach. Bleeding occurs in as many as 15% of people.[3]

Diet does not play an important role in either causing or preventing ulcers.[5] Treatment includes stopping smoking, stopping NSAIDs, stopping alcohol, and medications to decrease stomach acid. The medication used to decrease acid is usually either a proton pump inhibitor (PPI) or an H2 blocker with four weeks of treatment initially recommended.[1] Ulcers due to H. pylori are treated with a combination of medications such as amoxicillin, clarithromycin, and a PPI. Antibiotic resistance is increasing and thus treatment may not always be effective.[6] Bleeding ulcers may be treated by endoscopy, with open surgery typically only used in cases in which it is not successful.[3]

Peptic ulcers are present in around 4% of the population.[1] About 10% of people develop a peptic ulcer at some point in their life.[7] They resulted in 301,000 deaths in 2013 down from 327,000 deaths in 1990.[8] The first description of a perforated peptic ulcer was in 1670 in Princess Henrietta of England.[3]H. pylori was first identified as causing peptic ulcers by Barry Marshall and Robin Warren in the late 20th century,[6] a discovery for which they received the Nobel Prize in 2005.[9]

In patients over 45 with more than two weeks of the above symptoms, the odds for peptic ulceration are high enough to warrant rapid investigation by esophagogastroduodenoscopy.

The timing of the symptoms in relation to the meal may differentiate between gastric and duodenal ulcers: A gastric ulcer would give epigastric pain during the meal, as gastric acid production is increased as food enters the stomach. Symptoms of duodenal ulcers would initially be relieved by a meal, as the pyloric sphincter closes to concentrate the stomach contents, therefore acid is not reaching the duodenum. Duodenal ulcer pain would manifest mostly 2–3 hours after the meal, when the stomach begins to release digested food and acid into the duodenum.

Also, the symptoms of peptic ulcers may vary with the location of the ulcer and the patient's age. Furthermore, typical ulcers tend to heal and recur and as a result the pain may occur for few days and weeks and then wane or disappear.[11] Usually, children and the elderly do not develop any symptoms unless complications have arisen.

Burning or gnawing feeling in the stomach area lasting between 30 minutes and 3 hours commonly accompanies ulcers. This pain can be misinterpreted as hunger, indigestion or heartburn. Pain is usually caused by the ulcer but it may be aggravated by the stomach acid when it comes into contact with the ulcerated area. The pain caused by peptic ulcers can be felt anywhere from the navel up to the sternum, it may last from few minutes to several hours and it may be worse when the stomach is empty. Also, sometimes the pain may flare at night and it can commonly be temporarily relieved by eating foods that buffer stomach acid or by taking anti-acid medication.[12] However, peptic ulcer disease symptoms may be different for every sufferer.[13]

Perforation (a hole in the wall of the gastrointestinal tract) often leads to catastrophic consequences if left untreated. Erosion of the gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal content into the abdominal cavity. Perforation at the anterior surface of the stomach leads to acute peritonitis, initially chemical and later bacterial peritonitis. The first sign is often sudden intense abdominal pain; an example is Valentino's syndrome, named after the silent-film actor who experienced this pain before his death. Posterior wall perforation leads to bleeding due to involvement of gastroduodenal artery that lies posterior to the 1st part of duodenum.

A major causative factor (60% of gastric and up to 50-75%[15] of duodenal ulcers) is chronic inflammation due to Helicobacter pylori that colonizes the antralmucosa.[16] The immune system is unable to clear the infection, despite the appearance of antibodies. Thus, the bacterium can cause a chronic active gastritis (type B gastritis). Gastrin stimulates the production of gastric acid by parietal cells. In H. pylori colonization responses to increased gastrin, the increase in acid can contribute to the erosion of the mucosa and therefore ulcer formation.

Another major cause is the use of NSAIDs. The gastric mucosa protects itself from gastric acid with a layer of mucus, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the function of cyclooxygenase 1 (cox-1), which is essential for the production of these prostaglandins. COX-2 selective anti-inflammatories (such as celecoxib or the since withdrawn rofecoxib) preferentially inhibit cox-2, which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration.

Stress due to serious health problems such as those requiring treatment in an intensive care unit is well described as a cause of peptic ulcers, which are termed stress ulcers.[4]

While chronic life stress was once believed to be the main cause of ulcers this is no longer the case.[17] It is, however, still occasionally believed to play a role.[17] This may be by increasing the risk in those with other causes such as H. pylori or NSAID use.[18]

Dietary factors such as spice consumption, were hypothesized to cause ulcers until late in the 20th century, but have been shown to be of relatively minor importance.[19] Caffeine and coffee, also commonly thought to cause or exacerbate ulcers, appear to have little effect.[20][21] Similarly, while studies have found that alcohol consumption increases risk when associated with H. pylori infection, it does not seem to independently increase risk. Even when coupled with H. pylori infection, the increase is modest in comparison to the primary risk factor.[22][23][nb 1]

Although some studies have found correlations between smoking and ulcer formation,[24] others have been more specific in exploring the risks involved and have found that smoking by itself may not be much of a risk factor unless associated with H. pylori infection.[22][25][26][nb 2]

The diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors may treat ulcers without diagnosing them with specific tests and observe whether the symptoms resolve, thus indicating that their primary diagnosis was accurate.

Confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrast x-rays. The tests are typically ordered if the symptoms do not resolve after a few weeks of treatment, or when they first appear in a person who is over age 45 or who has other symptoms such as weight loss, because stomach cancer can cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduce acid.[11]

An esophagogastroduodenoscopy (EGD), a form of endoscopy, also known as a gastroscopy, is carried out on patients in whom a peptic ulcer is suspected. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.

One of the reasons that blood tests are not reliable for accurate peptic ulcer diagnosis on their own is their inability to differentiate between past exposure to the bacteria and current infection. Additionally, a false negative result is possible with a blood test if the patient has recently been taking certain drugs, such as antibiotics or proton pump inhibitors.[27]

The breath test uses radioactive carbon to detect H. pylori.[28] To perform this exam the patient will be asked to drink a tasteless liquid which contains the carbon as part of the substance that the bacteria breaks down. After an hour, the patient will be asked to blow into a bag that is sealed. If the patient is infected with H. pylori, the breath sample will contain radioactive carbon dioxide. This test provides the advantage of being able to monitor the response to treatment used to kill the bacteria.

The possibility of other causes of ulcers, notably malignancy (gastric cancer) needs to be kept in mind. This is especially true in ulcers of the greater (large) curvature of the stomach; most are also a consequence of chronic H. pylori infection.

If a peptic ulcer perforates, air will leak from the inside of the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to "free gas" within the peritoneal cavity. If the patient stands erect, as when having a chest X-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease.

Gastric ulcers are most often localized on the lesser curvature of the stomach. The ulcer is a round to oval parietal defect ("hole"), 2 to 4 cm diameter, with a smooth base and perpendicular borders. These borders are not elevated or irregular in the acute form of peptic ulcer, regular but with elevated borders and inflammatory surrounding in the chronic form. In the ulcerative form of gastric cancer the borders are irregular. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring.

A gastric peptic ulcer is a mucosal defect which penetrates the muscularis mucosae and lamina propria, produced by acid-pepsin aggression. Ulcer margins are perpendicular and present chronic gastritis. During the active phase, the base of the ulcer shows 4 zones: inflammatory exudate, fibrinoid necrosis, granulation tissue and fibrous tissue. The fibrous base of the ulcer may contain vessels with thickened wall or with thrombosis.[29]

When H. pylori infection is present, the most effective treatments are combinations of 2 antibiotics (e.g. clarithromycin, amoxicillin, tetracycline, metronidazole) and a proton pump inhibitor (PPI), sometimes together with a bismuth compound. In complicated, treatment-resistant cases, 3 antibiotics (e.g. amoxicillin + clarithromycin + metronidazole) may be used together with a PPI and sometimes with bismuth compound. An effective first-line therapy for uncomplicated cases would be amoxicillin + metronidazole + pantoprazole (a PPI).

Treatment of H. pylori usually leads to clearing of infection, relief of symptoms and eventual healing of ulcers. Recurrence of infection can occur and retreatment may be required, if necessary with other antibiotics. Since the widespread use of PPI's in the 1990s, surgical procedures (like "highly selective vagotomy") for uncomplicated peptic ulcers became obsolete.[citation needed]

The lifetime risk for developing a peptic ulcer is approximately 10%.[7] They resulted in 301,000 deaths in 2013 down from 327,000 deaths in 1990.[8]

In Western countries the percentage of people with Helicobacter pylori infections roughly matches age (i.e., 20% at age 20, 30% at age 30, 80% at age 80 etc.). Prevalence is higher in third world countries where it is estimated at about 70% of the population, whereas developed countries show a maximum of 40% ratio. Overall, H. pylori infections show a worldwide decrease, more so in developed countries. Transmission is by food, contaminated groundwater, and through human saliva (such as from kissing or sharing food utensils).[32]

A minority of cases of H. pylori infection will eventually lead to an ulcer and a larger proportion of people will get non-specific discomfort, abdominal pain or gastritis.

Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century, when epidemiological trends started to point to an impressive fall in its incidence.[33] The reason that the rates of peptic ulcer disease decreased is thought to be the development of new effective medication and acid suppressants and the discovery of the cause of the condition, H. pylori.

The incidence of duodenal ulcers has dropped significantly during the last 30 years, while the incidence of gastric ulcers has shown a small increase, mainly caused by the widespread use of NSAIDs. The drop in incidence is considered to be a cohort-phenomenon independent of the progress in treatment of the disease. The cohort-phenomenon is probably explained by improved standards of living which has lowered the incidence of H. pylori infections.[34]

The H. pylori hypothesis was initially poorly received,[38] so in an act of self-experimentation Marshall drank a Petri dish containing a culture of organisms extracted from a patient and five days later developed gastritis. His symptoms disappeared after two weeks, but he took antibiotics to kill the remaining bacteria at the urging of his wife, since halitosis is one of the symptoms of infection.[39] This experiment was published in 1984 in the Australian Medical Journal and is among the most cited articles from the journal.

In 1997, the Centers for Disease Control and Prevention, with other government agencies, academic institutions, and industry, launched a national education campaign to inform health care providers and consumers about the link between H. pylori and ulcers. This campaign reinforced the news that ulcers are a curable infection, and that health can be greatly improved and money saved by disseminating information about H. pylori.[40]

Some believed that mastic gum, a tree resin extract, actively eliminates the H. pylori bacteria.[41] However, multiple subsequent studies have found no effect of using mastic gum on reducing H. pylori levels.[42][43]

^Sonnenberg in his study cautiously concludes that, among other potential factors that were found to correlate to ulcer healing, "moderate alcohol intake might [also] favor ulcer healing." (p. 1066)

^Kurata 1997 explains that "Data in Fig. 8 indicate that 89% of all serious upper GI disease can be accounted for by NSAIDs and H. pylori, with cigarette smoking acting as a synergistic co-factor."(14)